Nanoparticle-based contrast agents for molecular imaging became a mainstay imaging tool for selectively detecting and imaging biological processes and diseases. The use of the enhanced scattering properties of gold nanoparticles as near infrared (NIR) contrast agents is under intensive investigation. This promising field builds on the safety of nonionizing radiation, ease of generation, relatively high tissue penetration depth, and reduced auto-fluorescence of the tissue in this spectral range. In addition, the particles' superior absorption properties have been utilized for photothermal therapy.
The Diffusion Reflection (DR)-based medical imaging method is very attractive since it is non-ionizing, low cost, convenient to generate and detect, and highly sensitive to the optical properties of the tissue. In the last decade, several diagnostic methods were developed based on DR measurements. For example, Yang et al., 2001, suggested UV reflectance spectroscopy for DNA and protein changes probing in human breast tissues. Zhu et al. 2006, presented method for diagnosis of breast cancer using DR spectroscopy, where a physical model (Monte Carlo inverse model) and an empirical model (partial least squares analysis) based approaches were compared for extracting diagnostic features from, the diffuse reflectance spectra. Cerussi et at, 2011, presented diffuse optical spectroscopic imaging (DOSI), which enables the measurement of tissue hemoglobin, water and lipid. Still, as many other spectroscopic methods, the DR technique suffers from multiple scattering which dominates light propagation in tissue. Therefore, a diagnostic tool which can diminish the scattering interruption on the DR signal is desired.
Despite recent therapeutic advances, atherosclerosis and its major vascular complications—myocardial infarction and ischemic cerebrovascular accident remain a leading cause of premature morbidity and mortality. Over the last decades, non-invasive methods have been developed in order to detect atherosclerotic disease before it becomes symptomatic. These have included anatomical imaging techniques such as coronary calcium scoring by Computed Tomography (CT), carotid intimal media thickness (IMT) measurement by ultrasound, and magnetic resonance imaging (MRI). The measurement of various biological markers is also available such as: lipoprotein subclass analysis, hs-CRP, and other inflammatory marker levels. Although there is a rapid progression in imaging techniques, the identification of early, inflamed “active” lesions within the coronary circulation, remains elusive due to small plaque size, cardiac and respiratory motion, and lack of a suitable tracer/marker specific for the unstable plaque. Furthermore, anatomic detection methods are generally more expensive, and the physiologic methods do not quantify the current state of the disease accurately enough to track its progression, in addition, invasive methods, such as angiography, demonstrate changes in the lumen, but not disease within the vessel wall Development of a new, easy to use, and non-invasive method at low cost, to locate atherosclerotic vascular disease (ASVD) at its early stages is desired.
Current imaging techniques are limited to detect early ASVD. Invasive techniques such as angiography have been widely employed to visualize the inside, or lumen, of blood vessels, with particular emphasis on the coronary arteries. Another invasive technique is the intravascular ultrasound (IVUS) that provides cross-sectional images of blood vessels, having the ability to detect and characterize atherosclerotic plaque. Non-invasive CT angiography can also detect significant narrowing and occluding processes in the lumens of various blood vessels. However, these methods focus on detecting significant luminal narrowing, and to a lesser extern on characterizing the underlying ASVD disease.
The ASVD plaques are divided into two broad categories: stable and unstable (also called vulnerable plaques). Stable atherosclerotic plaques tend to be rich in extracellular matrices and smooth muscle cells, while unstable plaques are rich in macrophages, foam cells and inflammatory cells, and usually have a weak fibrous cap. The unstable plaques are prone to rupture into the circulation, inducing thrombus formation in the lumen. Therefore, their detection is critical. One of the most common and fatal complications of ASVD is ruptured unstable plaque followed by thrombotic occlusion, causing myocardial infarction. Meanwhile, there is no reliable method that can distinguish between these two kinds of plaques or detect unstable plaques, prone to rupture.